Medical devices and methods of making the same

ABSTRACT

Medical devices, such as stents, and methods of making the devices are disclosed. In some embodiments, a medical device includes an alloy having tantalum, tungsten, zirconium and niobium. For example, the alloy can include from about 20% to about 40% by weight of tantalum, from about 0.5% to about 9% by weight of tungsten, and from about 0.5% to about 10% by weight of zirconium.

TECHNICAL FIELD

The invention relates to medical devices, such as stents, and methods ofmaking the devices.

BACKGROUND

The body includes various passageways such as arteries, other bloodvessels, and other body lumens. These passageways sometimes becomeoccluded or weakened. For example, the passageways can be occluded by atumor, restricted by plaque, or weakened by an aneurysm. When thisoccurs, the passageway can be reopened or reinforced, or even replaced,with a medical endoprosthesis. An endoprosthesis is typically a tubularmember that is placed in a lumen in the body. Examples of endoprosthesesinclude stents, stent-grafts, and covered stents.

An endoprosthesis can be delivered inside the body by a catheter thatsupports the endoprosthesis in a compacted or reduced-size form as theendoprosthesis is transported to a desired site. Upon reaching the site,the endoprosthesis is expanded, for example, so that it can contact thewalls of the lumen.

When the endoprosthesis is advanced through the body, its progress canbe monitored, e.g., tracked, so that the endoprosthesis can be deliveredproperly to a target site. After the endoprosthesis is delivered to thetarget site, the endoprosthesis can be monitored to determine whether ithas been placed properly and/or is functioning properly. Methods oftracking and monitoring a medical device include X-ray fluoroscopy andmagnetic resonance imaging (MRI).

SUMMARY

The invention relates to medical devices, such as stents, and methods ofmaking the medical devices.

In one aspect, the invention features a medical device including analloy having tantalum, niobium, tungsten and zirconium. The alloy has abalance of physical properties and mechanical properties that make itwell suited for medical device applications. For example, the alloy haslow magnetic susceptibility so as to have reduced image voids ordistortions during magnetic resonance imaging, and a good balance ofradiopacity (e.g., not too bright in radiography images so as to obscurevisibility of stented lumen features while using computed tomography(CT) or fluoroscopy imaging). As a result, magnetic resonance imaging,radiographic diagnostic imaging and angiography can be performed with amedical device including the alloy. At the same time, the alloy hasmechanical properties, such as yield strength, ultimate tensilestrength, ductility, stiffness, fatigue strength and toughness, thatallow it to be processed and formed into a medical device, and to beused as a medical device. The alloy may also exhibit corrosionresistance and biocompatibility that are useful for many medical deviceapplications.

Embodiments may include one or more of the following features. The alloyincludes from about 20% to about 40% by weight of tantalum. The alloyincludes from about 0.5% to about 9% by weight of tungsten. The alloyincludes from about 0.5% to about 10% by weight of zirconium. The alloyincludes from about 41% to about 79% by weight of niobium. The alloyincludes from about 20% to about 40% by weight of tantalum, from about0.5% to about 9% by weight of tungsten, and from about 0.5% to about 10%by weight of zirconium. The alloy further includes a balance of niobium.The alloy includes from about 1% to about 19% by weight of tungstenand/or zirconium. The alloy further includes an element selected fromthe group consisting of molybdenum, rhenium, iridium, and hafnium.

The alloy may have one or more of the following properties. The alloymay have a Young's (elastic) modulus of from about 10 million psi toabout 30 million psi. The alloy may have a yield strength of from about20 thousand to about 60 thousand psi. The alloy may have a percentelongation of from about 10% to about 40% to fracture.

The medical device may further include a filament having at least aportion including the alloy.

The medical device may further include a tubular member including thealloy.

The medical device may further include a multilayered structure, whereinat least one layer includes the alloy. The multilayered structure may bein the form of a tubular member or a filament.

The medical device can be constructed in a variety of forms. The medicaldevice can be adapted to be implanted in a body, for example, by beingin the form of a stent. The medical device can be in the form of aneedle, a catheter, a guidewire, an orthopedic implant, an intraluminalfilter, or a dental prosthesis. The medical device can be in the form offorceps, clamps, or fixtures.

In another aspect, the invention features a medical device including analloy consisting or consisting essentially of tantalum, tungsten,zirconium and niobium.

Embodiments may include one or more of the following features.

In another aspect, the invention features a method of making a medicaldevice. The method includes forming an alloy as described herein, andusing the alloy to form the medical device, wholly or in part.

In another aspect, the invention features an alloy composition asdescribed herein.

As used herein, an alloy is a homogeneous substance including two ormore metals or a metal and nonmetal intimately united, such as by beingfused together or dissolving in each other when molten, and remainingfused together or dissolved in each other when solid.

The concentrations described herein are expressed in weight percents.

Other aspects, features, and advantages will be apparent from thedescription of the preferred embodiments thereof and from the claims.

DESCRIPTION OF DRAWINGS

FIG. 1 is a perspective view of an embodiment of a stent.

FIG. 2 is a cross-sectional view of an embodiment of a multilayeredwire.

FIG. 3 is a perspective view of an embodiment of a multilayered tube.

DETAILED DESCRIPTION

Referring to FIG. 1, a stent 20 has the form of a tubular member definedby a plurality of bands 22 and a plurality of connectors 24 that extendbetween and connect adjacent bands. During use, bands 22 are expandedfrom an initial, small diameter to a larger diameter to contact stent 20against a wall of a vessel, thereby maintaining the patency of thevessel. Connectors 24 provide stent 20 with flexibility andconformability so that the stent can adapt to the contours of thevessel.

Stent 20 includes (e.g., is formed of) a biocompatible alloy compositionthat is capable of providing stent 20 with a balance of physicalproperties and mechanical properties that enhances the performance ofthe stent. For example, the alloy composition includes relatively denseelements, such as tantalum and tungsten, that enhance the radiopacity ofstent 20; as a result, the stent can be easily detected during X-rayfluoroscopy and CT. The alloy composition also includes elements, suchas niobium, that have low magnetic susceptibility; as a result, stent 20can be compatible with MRI techniques, e.g., by not producingsubstantial amounts of magnetic artifacts, image distortions or voids,and/or by not heating or moving during imaging.

At the same time, as described below, the alloy composition hasmechanical properties that allow it to be processed and formed into amedical device, and to provide the device with good mechanicalperformance. For example, the alloy composition has a strength andductility such that it can be cold worked to form a tube from whichstent 20 can be formed. The alloy composition can also have a stiffnessor elastic modulus to provide stent 20 with reduced recoil, e.g., whenthe stent is crimped on a delivery catheter or when the stent isexpanded against a vessel wall.

The alloy composition includes an intimate combination (e.g., a solidsolution) of tantalum, tungsten, zirconium, and niobium. Niobium, whichis a low magnetic susceptibility material, makes up the greatest portionof the alloy composition. The other elements, which have good solubilityin niobium, are believed to further contribute to the mechanical and/orphysical properties of the alloy composition, without substantially andadversely affecting the magnetic susceptibility of the composition. Insome embodiments, the alloy composition further includes molybdenum,rhenium, iridium, and/or hafnium, in any combination.

Tungsten and zirconium are capable of strengthening the alloycomposition, e.g., by solid solution strengthening. In addition,tungsten is also capable of enhancing the radiopacity of the alloycomposition. The concentrations of the tungsten and zirconium areselected to provide one or more targeted mechanical properties(described below). In some embodiments, the alloy composition includesfrom about 0.1% to about 25% by weight of tungsten and zirconium, in anyratio. For example, of the total amount of tungsten and zirconium in thealloy composition, the alloy composition can include greater than orequal to about 0%, about 10%, about 20%, about 30%, about 40%, about50%, about 60%, about 70%, about 80%, or about 90% of tungsten, with theremainder being zirconium; and/or less than or equal to about 100%,about 90%, about 80%, about 70%, about 60%, about 50%, about 40%, about30%, about 20%, or about 10% of tungsten, with the remainder beingzirconium. The alloy composition can include greater than or equal toabout 0.1%, about 1%, about 3%, about 5%, about 7%, about 9%, about 11%,about 13%, about 15%, about 17%, about 19%, about 21%, or about 23% byweight of tungsten and/or zirconium; and/or less than or equal to about25%, about 23%, about 21%, about 19%, about 17%, about 15%, about 13%,about 11%, about 9%, about 7%, about 5%, about 3%, or about 1% by weightof tungsten and/or zirconium. In some embodiments, the alloy compositioncan include from about 0.1% to about 15% by weight of tungsten, and fromabout 0.1% to about 10% by weight of zirconium. The concentration oftungsten can be greater than or equal to about 0.1%, about 1%, about 3%,about 5%, about 7%, about 9%, about 11%, or about 13% by weight; and/orless than or equal to about 15%, about 13%, about 11%, about 9%, about7%, about 5%, about 3%, or about 1% by weight. The concentration ofzirconium can be greater than or equal to about 0.1%, about 2%, about4%, about 6%, or about 8% by weight; and/or less than or equal to about10%, about 8%, about 6%, about 4%, or about 2% by weight.

Tantalum is capable of increasing the radiopacity of the alloycomposition and strengthening the composition, albeit less so thantungsten and zirconium. Tantalum can also enhance the ductility of thealloy composition so that the composition can be conveniently worked.The concentration of tantalum in the alloy composition can be from about0.1% to about 40% by weight. For example, the concentration of tantalumcan be greater than or equal to about 0.1%, about 2%, about 4%, about6%, about 8%, about 10%, about 12%, about 14%, about 16%, about 18%,about 20%, about 22%, about 24%, about 26%, about 28%, about 30%, about32%, about 34%, about 36%, or about 38% by weight; and/or less than orequal to about 40%, about 38%, about 36%, about 34%, about 32%, about30%, about 28%, about 26%, about 24%, about 22%, about 20%, about 18%,about 16%, about 14%, about 12%, about 10%, about 8%, about 6%, about4%, or about 2% by weight.

In some embodiments, the alloy composition further includes one or more(e.g., two, three or four) elements selected from the group consistingof molybdenum, rhenium, iridium, and hafnium. These elements have atomicsizes and solubility characteristics that allow them to form a solidsolution with niobium. These elements can also enhance the mechanicalproperties of the alloy composition, e.g., by increasing the elasticmodulus. These elements can be incorporated into the alloy compositionto replace a portion of or all of the tantalum, zirconium, and/ortungsten, in any combination.

Rhenium and molybdenum are highly potent strengtheners and may be addedto the alloy to increase the yield strength and ultimate tensilestrength by solid solution strengthening. In some embodiments, the alloyincludes from about 0.5% to about 5% by weight of rhenium and/ormolybdenum. The alloy may include greater than or equal to about 0.5%,about 1%, about 2%, about 3%, or about 4% by weight of rhenium and/ormolybdenum; and/or less than or equal to about 5%, about 4%, about 3%,about 2%, or about 1% by weight of rhenium and/or molybdenum. Of thetotal amount of rhenium and molybdenum in the alloy, rhenium can bepresent from about 0% to 100%, with the remainder being molybdenum,similar to that described above for tungsten and zirconium. Inembodiments including rhenium and/or molybdenum, the tantalumconcentration is as described above to enhance elastic modulus andradiopacity. The niobium concentration can be reduced to compensate forthe rhenium and molybdenum additions, and the concentrations of tungstenand zirconium can be as described above or reduced to about one-half oftheir concentrations in an alloy that does not contain rhenium and/ormolybdenum. For example, if there were about 3.5% tungsten and about1.3% zirconium in an alloy that does not contain Re and Mo, then theremay be about 1.8% tungsten and about 0.6% zirconium in an alloy thatincludes Re and Mo additions.

Iridium, which has an elastic modulus of about 76 million psi, can beadded to the alloy to increase the modulus (stiffness) of the alloy, andto enhance hot workability and ductility. Iridium is soluble in tantalum(e.g., up to about 5%) and niobium (e.g., up to about 12%). In someembodiments, iridium is added to up to 5% of the tantalum concentrationin the alloy. In other embodiments, the alloy includes from about 0.5%to about 8% by weight of iridium. For example, the iridium concentrationcan be greater than or equal to about 0.5%, about 1%, about 2%, about3%, about 4%, about 5%, about 6%, or about 7% by weight; and/or lessthan or equal to about 8%, about 7%, about 6%, about 5%, about 4%, about3%, about 2%, or about 1% by weight.

Hafnium may be added to enhance the hot workability, ductility andstiffness of the alloy. Hafnium can act as a grain boundary strengthenerat elevated temperatures, and as a result, the alloy may be less likelyto tear at the grain boundaries during hot working operations. Forexample, hafnium may react with trace carbon in the starting materialsto form hafnium carbides in the matrix of the alloy so that the carbondoes not react with niobium and/or tantalum to form excessive amounts ofniobium carbides and/or tantalum carbides along grain boundaries. Thecarbides in the grain boundaries can reduce grain boundary ductility andincrease the alloy susceptibility to intergranular failure. Hafnium,which is soluble to about 18% by weight in niobium and to 5% intantalum, can be added in the range of about 1% to about 12%. Forexample, the hafnium concentration can be greater than or equal to about1%, about 3%, about 5%, about 7%, about 9%, or about 11% by weight;and/or less than or equal to about 12%, about 10%, about 8%, about 6%,about 4%, or about 2% by weight. In some embodiments, hafnium is addedup to 5% of the tantalum concentration.

Titanium, which is well soluble in niobium and tantalum but has arelatively low elastic modulus, may be added to enhance the stiffness,hot workability and ductility of niobium. In particular, since some ofthe other elements that may be present in the alloy serve to increasethe strength of the alloy, titanium may be added to provide a balancebetween strength and ductility. In some embodiments, titanium is presentin the range of from about 0.5% to about 20%, such as from about 1% toabout 10%, by weight. For example, the titanium concentration can begreater than or equal to about 0.5%, about 2%, about 4%, about 6%, about8%, about 10%, about 12%, about 14%, about 16%, or about 18% by weight;and/or less than or equal to about 20%, about 18%, about 16%, about 14%,about 12%, about 10%, about 8%, about 6%, about 4%, or about 2% byweight.

Niobium makes up the balance of the alloy composition, e.g., afteraccounting for the other elements in the alloy described above. Incertain embodiments, the alloy composition includes from about 41% toabout 79% by weight of niobium. For example, the alloy composition caninclude greater than or equal to about 41%, about 45%, about 50%, about55%, about 60%, about 65%, about 70%, or about 75% by weight of niobium;and/or less than or equal to about 79%, about 75%, about 70%, about 65%,about 60%, about 55%, about 50%, or about 45% by weight of niobium.

As indicated above, in addition to having the above amounts of elements,the alloy composition can also have certain mechanical and physicalproperties that enhance the performance of the medical device in whichthe alloy composition is incorporated. For example, to form an ingot ofthe alloy composition into a feedstock of raw material (such as a tube),the alloy composition may have certain tensile properties (e.g., yieldstrength and ductility) and grain structure (e.g., equiaxed) that allowit to be processed (e.g., cold worked). In some embodiments, the alloycomposition has a percent elongation in a room temperature tensile testof from about 10% to about 40% to fracture. For example, the percentelongation can be greater than or equal to about 10%, about 15%, about20%, about 25%, about 30%, or about 35%; and/or less than or equal toabout 40%, about 35%, about 30%, about 25%, about 20%, or about 15%. Theyield strength and elastic modulus of the alloy composition are targetedto reduce recoil, e.g., when stent 20 is crimped or expanded. In someembodiments, the Young's (elastic) modulus from a room temperaturetensile test is from about 10 msi (million psi) to 30 msi. The elasticmodulus can be greater than or equal to about 10 million psi, about 15million psi, about 20 million psi, or about 25 million psi; and/or lessthan or equal to about 30 million psi, about 25 million psi, about 20million psi, or about 15 million psi. In some embodiments, the yieldstrength is from about 20 ksi to about 60 ksi. For example, the yieldstrength can be greater than or equal to about 20 ksi (thousand psi),about 25 ksi, about 30 ksi, about 35 ksi, about 40 ksi, about 45 ksi,about 50 ksi, or about 55 ksi; and/or less than or equal to about 60ksi, about 55 ksi, about 50 ksi, about 45 ksi, about 40 ksi, about 35ksi, about 30 ksi, or about 25 ksi.

As examples, referring to Table 1, some mechanical properties of thealloys described herein are shown. The alloys have high yield strengths(e.g., comparable to 316L stainless steel), high moduli, and highelongation to allow cold forming.

TABLE 1 0.2% Offset Modulus (E), Yield Strength, UTS, Material: msi ksiksi % elongation Nb—28Ta—3.5W—1.3Zr 19 51 69 17Nb—10Hf—1Ti—0.7Zr—0.5Ta—0.5W 16 45 62 23

The physical properties of the alloy composition that relate to magneticresonance and radiographic imaging include its magnetic susceptibilityand radiopacity. For MRI compatibility and safety, the alloy isformulated to reduce signal distortion and movement within the body ornerve simulation, by controlling the magnetic susceptibility andsolubility of the alloy constituents. In some embodiments, the magneticsusceptibility of the alloy is less than the magnetic susceptibility ofaustenitic stainless steel (such as 316L stainless steel), e.g. in thesame order of magnitude as titanium (about 10⁻⁴).

For radiopacity, the alloy is formulated to a desired mass absorptioncoefficient. Radiopacity is proportional to mass absorption coefficientand thickness. Higher material mass absorption coefficient and/orthickness may increase the radiopacity of a medical device. Theradiopacity of a device is preferably sufficient for viewing but not toobright. For example, in some cases, the radiopacity of stents made ofpure tantalum may be too high because X-ray image artifact, such as ahalo about the stent, is produced. In embodiments, the stent is readilyvisible by fluoroscopy and CT, but does not appear so bright that detailadjacent to or within the lumen of the medical device in thefluoroscopic image is obscured or distorted. In some embodiments, thealloy of the medical device has a radiopacity (brightness in an X-rayfilm image) of from about 1.10 to about 3.50 times (e.g., greater thanor equal to about 1.1, about 1.5, about 2.0, about 2.5, or about 3.0times; and/or less than or equal to about 3.5, about 3.0, about 2.5,about 2.0, or about 1.5 times) that of the same medical device made from316L grade stainless steel, as measured by ASTM F640 (Standard TestMethods for Radiopacity of Plastics for Medical Use). Furthermore, as aresult of the increased radiopacity provided by the alloy composition,the thickness of the medical device can be reduced, e.g., relative to316L stainless steel. In embodiments in which the medical deviceincludes a stent, thinner stent walls provide the stent with enhancedflexibility and reduced profile. Mass absorption coefficients anddensities for Nb, Ta, W, Zr, Mo, Re, Ir, and Hf at 0.050 MeV are listedin the Table 2 below.

TABLE 2 Metal Nb Ta W Zr Mo Re Ir Hf Mass 6.64 5.72 5.95 6.17 7.04 6.216.69 5.48 absorption coefficient, cm²/g Density, g/cc 8.57 16.7 19.3 6.510.2 21.0 22.65 13.1

In embodiments, the mass absorption coefficient of the alloy is fromabout 5.00 cm²/g to about 7.00 cm²/g at 0.050 MeV. Mass absorptioncoefficient can be calculated from the results of radiopacity tests, asdescribed in The Physics of Radiology, H. E. Johns, J. R. Cunningham,Charles C. Thomas Publisher, 1983, Springfield, Ill., pp. 133-143.

The alloys can be synthesized by intimately combining the components ofthe alloys. In some embodiments, samples of an alloy composition aremade by melting charges of the components to form a homogeneous alloy.The targeted alloy composition can be formed by melting the elementalstarting materials (such as chips, powders, balls, pellets, bars, wires,and/or rods) in the concentrations described above. Melting can beperformed in an inert atmosphere (e.g., argon pressure), in a partialpressure (in argon at a pressure less than atmospheric) or under vacuumusing vacuum induction melting (VIM), vacuum arc remelting (VAR),electron beam melting (EBM), plasma melting, vacuum or inert gas plasmadeposition, hot isostatic pressing, and/or cold pressing and sintering.The raw samples (initial form of the alloy) can be in the form of aningot, a compact, or a deposit. The raw sample can then be formed, forexample, into a billet using metallurgical techniques, such as pressing,forging, drawing, rolling, and extruding. The billet can be drawn intotubing or rolled into a sheet for stock stent tubing production.

In some embodiments, the tube that makes up the tubular member of stent20 can be formed using metallurgical techniques, such asthermomechanical processes. For example, a hollow metallic member (e.g.,a rod or a bar) of the alloy composition can be drawn through a seriesof dies to plastically deform the member to a targeted size and shape.The plastic deformation strain can harden the member (and increases itsyield strength) and elongates the grains along the longitudinal axis ofthe member. Other methods include ingot metallurgy, extrusion and barrolling, seamless tube drawing, and mechanical, laser or chemicalmachining. The deformed member can be heat treated (e.g., annealed abovethe recrystallization temperature and/or hot isostatically pressed) totransform the elongated grain structure into an initial grain structure,e.g., one including equiaxed grains.

Next, bands 22 and connectors 24 of stent 20 are formed, for example, bymachining the tube. Selected portions of the tube can be removed to formbands 22 and connectors 24 by laser or waterjet cutting, as described inU.S. Pat. No. 5,780,807, hereby incorporated by reference in itsentirety. In certain embodiments, during laser cutting, a liquidcarrier, such as a solvent or an oil, is flowed through the lumen of thetube. The carrier can prevent dross formed on one portion of the tubefrom re-depositing on another portion, and/or reduce formation of recastmaterial on the tube. Other methods of removing portions of the tube canbe used, such as mechanical machining (e.g., micro-machining),electrical discharge machining (EDM), and photoetching (e.g., acidphotoetching).

In some embodiments, after bands 22 and connectors 24 are formed, areasof the tube affected by the cutting operation above can be removed. Forexample, laser machining of bands 22 and connectors 24 can leave asurface layer of melted and resolidified material and/or oxidized metalthat can adversely affect the mechanical properties and performance ofstent 20. The affected areas can be removed mechanically (such as bygrit blasting or honing) and/or chemically (such as by etching orelectropolishing).

After the removal of areas of the tube affected by the cuttingoperation, the unfinished stent is finished. The unfinished stent can befinished, for example, by electropolishing to a smooth finish. In someembodiments, about 0.0001 inch of the stent material can be removed bychemical milling and/or electropolishing to yield a stent.

Stent 20 can be of any desired size and shape (e.g., coronary stents,aortic stents, peripheral vascular stents, gastrointestinal stents,urology stents, and neurology stents). Depending on the application,stent 20 can have a diameter of between, for example, 1 mm to 46 mm. Incertain embodiments, a coronary stent can have an expanded diameter offrom about 2 mm to about 6 mm. In some embodiments, a peripheral stentcan have an expanded diameter of from about 5 mm to about 24 mm. Incertain embodiments, a gastrointestinal and/or urology stent can have anexpanded diameter of from about 6 mm to about 30 mm. In someembodiments, a neurology stent can have an expanded diameter of fromabout 1 mm to about 12 mm. An abdominal aortic aneurysm (AAA) stent anda thoracic aortic aneurysm (TAA) stent can have a diameter from about 20mm to about 46 mm. A renal stent can have a diameter from about 8 mm toabout 12 mm.

Stent 20 can be used, e.g., delivered and expanded, using a catheterdelivery system. Catheter systems are described in, for example, WangU.S. Pat. No. 5,195,969, Hamlin U.S. Pat. No. 5,270,086, andRaeder-Devens, U.S. Pat. No. 6,726,712, which are incorporated herein byreference. Stents and stent delivery are also exemplified by the Radius®or Symbiot® systems, available from Boston Scientific Scimed, MapleGrove, Minn.

While a number of embodiments have been described above, the inventionis not so limited.

For example, the alloy compositions may further include oxygen, which issoluble in niobium and can have a potent effect on increasing yieldstrength. In some embodiments, the concentration of oxygen ranges fromabout 10 ppm to about 1,000 ppm, such as from about 50 ppm to about 300ppm.

The alloy compositions can be used in other stent designs. The alloycompositions can be formed into wires or filaments that are subsequentlyknitted, woven, or crocheted to form tubular structure of a stent.Knitted and woven stents are described, for example, in Heath, U.S. Pat.No. 5,725,570; and Andersen, U.S. Pat. No. 5,366,504; Mayer, U.S. Pat.No. 5,800,511; Sandock, U.S. Pat. No. 5,800,519; and Wallsten, U.S. Pat.No. 4,655,771.

Furthermore, while stent 20 is shown having a tubular member madeentirely of the alloy compositions described above, in otherembodiments, the alloy compositions can be used to form one or moreselected portions of a stent or other medical device. For example, astent can be formed from a multilayered wire or filament, a multilayeredsheet (e.g., rolled into a tube and joined at opposing edges), or amultilayered tube (e.g., by co-drawing multiple coaxial tubes), and oneor more of the layers can include the alloy compositions. Referring toFIG. 2, a multilayered wire 40 includes a middle layer 42 having anNb—Zr—W—Ta alloy composition as described herein, an outer layer 44, andan inner layer 46. Similarly, referring to FIG. 3, a multilayered stent48 can include a middle layer 50 having an alloy composition asdescribed herein, an outer layer 52, and an inner layer 54. Inembodiments, middle layers 42 and 50 are capable of enhancing the MRIcompatibility and radiopacity of wire 40. Outer and inner layers 44, 46,52, and 54, which can have the same composition or differentcomposition, can include any material suitable for medical deviceapplications, such as stainless steel (e.g., 316L and 304L stainlesssteel), radiopacity enhanced steels (e.g., as described inUS-2003-0018380-A1, US-2002-0144757-A1; and US-2003-0077200-A1), Nitinol(a nickel-titanium alloy), Elgiloy, L605 alloys, MP35N, Ti-6Al-4V,Ti-50Ta, Ti-10Ir, Nb-1Zr, and Co-28Cr-6Mo. Other materials includeelastic biocompatible metal such as a superelastic or pseudo-elasticmetal alloy, as described, for example, in Schetsky, L. McDonald, “ShapeMemory Alloys”, Encyclopedia of Chemical Technology (3rd ed.), JohnWiley & Sons, 1982, vol. 20. pp. 726-736; and commonly assigned U.S.Ser. No. 10/346,487, filed Jan. 17, 2003. Alternatively or additionallyto middle layers 42 and 50, the Nb—Zr—W—Ta alloy compositions can beincluded in other layers, such as the inner layer and/or the outerlayer. Multilayered wires and tubes are described, for example, inHeath, U.S. Pat. No. 5,725,570.

In other embodiments, short fibers of the alloy compositions can be usedto reinforce a matrix material, such as a polymeric material or anothermetallic material. Examples of medical devices having a matrixreinforced by fibers are described in Stinson, U.S. 2004-0044397.

Stent 20 can also be a part of a covered stent or a stent-graft. Inother embodiments, stent 20 can include and/or be attached to abiocompatible, non-porous or semi-porous polymer matrix made ofpolytetrafluoroethylene (PTFE), expanded PTFE, polyethylene, urethane,or polypropylene.

Stent 20 can include a releasable therapeutic agent, drug, or apharmaceutically active compound, such as described in U.S. Pat. No.5,674,242, U.S. Ser. No. 09/895,415, filed Jul. 2, 2001, and U.S. Ser.No. 10/232,265, filed Aug. 30, 2002. The therapeutic agents, drugs, orpharmaceutically active compounds can include, for example,anti-thrombogenic agents, antioxidants, anti-inflammatory agents,anesthetic agents, anti-coagulants, and antibiotics. Alternatively oradditionally, stent 20 can include one or more ceramic layers, such asniobium oxide and/or iridium oxide, as described in U.S. Pat. Nos.6,387,121 and 6,245,104, by anodizing or otherwise oxidizing the stent.The ceramic layer(s) can enhance surface passivity, and in embodimentsin which the layer(s) are porous, one or more drugs can be retained inthe layer(s) for delivery after implantation.

In other embodiments, the structures and methods described herein can beused to make other medical devices, such as other types ofendoprostheses, guidewires, hypotubes, catheters, distal protectiondevices, and abdominal aortic aneurysm repair devices. For example, thealloys can be used in filters such as removable thrombus filtersdescribed in Kim et al., U.S. Pat. No. 6,146,404; in intravascularfilters such as those described in Daniel et al., U.S. Pat. No.6,171,327; and vena cava filters such as those described in Soon et al.,U.S. Pat. No. 6,342,062. The alloys can also be used in guidewires suchas a Meier Steerable Guide Wire (for AAA stent procedure) and an ASAPAutomated Biopsy System described in U.S. Pat. Nos. 4,958,625,5,368,045, and 5,090,419.

The alloys can be used to form medical devices that benefit from havinghigh strength to resist overloading and fracture, good corrosionresistance, and/or biocompatibility (e.g., capable of being implanted ina body for long periods (such as greater than ten years)). Examples ofdevices include internal and external fixation devices, hip stems, kneetrays, dental prostheses, and needles.

The following examples are illustrative and not intended to be limiting.

EXAMPLE 1

This example describes synthesis of an alloy with a nominal compositionof Nb-28Ta-3.5W-1.3Zr.

The raw powder materials were weighed out to the desired proportions andmelted in an arc melter (Materials Research Furnaces ABJ-900). The Zrpowder was from Cerac; Z-1088, L/N X0027543, 99.8% pure; −140, +325mesh. The Ta powder was from Cerac; T-1201, L/N X25522, 99.9% pure,−140, +325 mesh. The Nb powder was from Cerac; N-1096, L/N X22690, 99.8%pure, −140, +325 mesh. The W powder was from Cerac; T-1166, L/NX0027060, 99.5% pure, −100, +200 mesh. The powders were weighed out andmixed in three bottles as indicated in Table 3.

TABLE 3 Charge Nb powder, Ta powder, W powder, Zr powder, No. gramsgrams grams grams (1) 31.8 13.5 2.0 0.6 (2) 31.9 13.4 1.4 0.7 (3) 31.113.4 1.5 0.6 Total Mass 94.8 40.3 4.9 1.9 Weight % 67 28 3.5 1.3

The powder from the charge bottles was poured into two ingot meltcavities in the arc melter. After the first melting operation, the tworesultant ingots were combined in the largest elongated ingot cavity forthe subsequent melting operations. A total of four melt operations wereperformed. The first was performed at 250A to melt the powder. Thesecond and third were performed at 400 amps to combine and repeatedlymelt the ingots. The fourth was performed at 250A to smoothen thesurface to make machining easier. The resultant ingot weighed 141.3grams.

The as-cast ingot was struck with a hammer ten times to see if thematerial had a level of ductility that would be suitable for machiningand cold rolling. The ingot did not crack or fracture. The ingot was cutinto three pieces in preparation for machining into rectangular bars(Table 4). One piece of the ingot (#3 below) was homogenized in a vacuumheat treat oven at 1200° C. for six hours prior to machining. This piecedid not crack or fracture when struck with the hammer following thehomogenization treatment.

TABLE 4 Length, Width, Thickness, Bar # inch inch inch 1 1.50 0.44 0.202 1.45 0.45 0.20 3 1.47 0.49 0.20

The three machined bars were cold rolled to a total of 50% reduction inthickness and then annealed at 1200° C. in vaccum for 60 minutes andvacuum cooled in a vacuum heat treat furnace. The dimensions of thestrips after cold rolling and heat treating were measured and found tobe 2.3″ long×0.11″ thick. The strip surfaces and edges were examinedwithout magnification. Strips 1 and 2 had fine surface fissures. Strip 3did not have any cracks or fissures.

The strips were cold rolled to a total of 50% reduction in thickness.The dimensions of the rolled strips are listed in Table 5. No cracks orfissures were observed on the strips.

TABLE 5 Length, Width, Thickness, Bar # inches inch inch 1 3.72 0.650.055 2 4.00 0.58 0.056 3 4.18 0.60 0.055

The three strips were annealed in the vacuum heat treat furnace at 1200°C. for 30 minutes in vaccum and vaccum cooled. The purpose of this heattreatment was to recrystallize the cold worked microstructure and tosoften the material for further cold rolling. The three strips were coldrolled to the following dimensions (Table 6).

TABLE 6 Length, Width, Thickness, Bar # inches inches inches 1 7.0 0.660.027 2 7.8 0.59 0.028 3 8.0 0.61 0.027The three strips were annealed in the vacuum heat treat furnace at 1200°C. for 30 minutes in vaccum and were vaccum cooled.

The three strips were then subjected to tensile specimen machining andtesting. Included in the testing for comparison was a strip of Nb-50Taalloy that was made with the arc melter and laboratory rolling mill(Sample X). Tensile data from commercially produced annealed Nb-50Tastrip (Heraeus) was included to allow comparison of laboratory arcmelted material to commercially produced material. The 0.020″ thickstrip was machined into flat specimens similar to ASTM E8 FIG. 1 (0.125inch width×0.02 inch thick×0.67 inch gage length). Testing was performedwith a 0.5″ extensometer gage length. The test specimen strain ratethrough 0.2% offset yield was 0.005 in./in./minute, and the crossheadextension rate was 0.02 inch/minute from yield to failure. Testing wasconducted at room temperature.

TABLE 7 0.2% Elongation, Modulus (E), UTS, YS, (%) from Sample Material:10⁶ psi ksi ksi gage marks Heraeus Commercial 19.9 47.1 35.1 23 Nb—50TaSample X Laboratory 18.6 66.0 53.5 20 Nb—50Ta Average of Laboratory 18.769.0 50.8 17 Samples #1-3 NbTaWZr

The average tensile strength, yield strength, % elongation, and modulusof the arc melted, rolled, and annealed Nb—Ta—W—Zr alloy strips wassimilar to that of the Nb-50Ta alloy made in a similar way. The arcmelted materials had higher strength and lower elongation that theHereaus Nb-50Ta strip, and this is hypothesized to be attributed tohigher oxygen concentration in the arc melted material relative to thecommercially processed material.

In particular, the tensile properties of the arc meltedNb-28Ta-3.5W-1.3Zr alloy strip were similar to the arc melted Nb-50Taalloy. This suggests that the solid solution strengthening from the Tain Nb can be accomplished by tungsten and zirconium additions instead ofonly Ta. In some cases, Nb-50Ta may be too highly radiopaque in stentwall thicknesses, and the Nb-28Ta-3.5W-1.3Zr alloy may provide a moredesirable level of radiopacity because the tantalum concentration islower. At the same time, the Nb-28Ta-3.5W-1.3Zr alloy has a good modulusand yield strength (e.g., relative to Nb-1Zr alloy, which may have ayield strength about 10 ksi less).

EXAMPLE 2

An ingot of the alloy was produced by vacuum arc remelting (VAR) ofelemental raw materials by MetalWerks (Aliquippa, Pa.). In particular,Ta, Nb, and Zr plate pieces, along with a W sheet, were welded in avacuum to form an electrode. The electrode was melted one time in a VARfurnace to make the ingot. The composition for the ingot as determinedis shown in Table 8. The ingot was 2.425″ in diameter, 6″ long, andweighed about 11.1 pounds.

TABLE 8 Ingot Composition Element Weight Percent Tantalum (Ta) 30.6Tungsten (W) 3.37 Zirconium (Zr) 1.36 Oxygen (O) 0.013 Nitrogen (N)0.010 Carbon (C) 0.0050 Hydrogen (H) 0.0006 Molybdenum (Mo) 0.010Titanium (Ti) <0.001 Silicon (Si) 0.003 Iron (Fe) 0.01 Nickel (Ni) 0.016Hafnium (Hf) Not tested Niobium (Nb) balance

The cylindrical ingot was axially drilled to produce a hollow cylinder(thick tube). The hollow cylinder was extruded to reduce diameter,increase length, and convert the as-cast microstructure to a wroughtmicrostructure. The extrusion was vacuum annealed (2000-2100F for 2hours) and pilgered to produce feedstock for tube mandrel drawing.Extrusion, pilgering, and mandrel drawing were performed by Noble-MetInc. (Salem, Va.).

Two pilgered tubes were mandrel drawn to 0.072″ OD×0.004″ ID tubing.Standard commercial processing was utilized and included intermediateannealing steps. Vacuum annealing for two hours at 2050° F. produced apartially recrystallized structure, and two hours at 2100° F. producedmostly recrystallized structure. Twelve tensile tests were performed onthe tubing in the 2100° F. annealed condition. Test speed was 0.02inches/minute through yield and 0.20 inches/minute from thereon tofailure. The results are listed in Table 9. The microstructure of the2100F annealed tubing consisted of fine equiaxed grains. The ASTM E112average grain size number G was determined by the comparison methodusing Plate IV to be 9.6.

TABLE 9 Tensile results for tubing in 2100° F. annealed condition TestModulus (E), 0.2% offset YS, UTS, Specimen: mpsi ksi ksi % elongationMean 17.5 43.0 62.2 25.9 Std Dev 0.6 1.8 0.7 1.8

All publications, references, applications, and patents referred toherein are incorporated by reference in their entirety.

Other embodiments are within the claims.

1. A stent, the stent comprising an alloy comprising from about 20% toabout 40% by weight of tantalum, from about 0.5% to about 9% by weightof tungsten, from about 0.5% to about 10% by weight of zirconium, fromabout 41% to about 79% by weight of niobium and from about 10 ppm toabout 1000 ppm oxygen.
 2. The stent of claim 1, wherein the alloyfurther comprises an element selected from the group consisting ofmolybdenum, rhenium, iridium, and hafnium.
 3. The stent of claim 1,further comprising a filament having at least a portion including thealloy.
 4. The stent of claim 1, further comprising a tubular membercomprising the alloy.
 5. The stent of claim 1, further comprising amultilayered structure, wherein at least one layer comprises the alloy.6. The stent of claim 5, wherein the multilayered structure is in theform of a tubular member or a filament.
 7. A stent, the stent comprisingan alloy comprising from about 20% to about 40% by weight of tantalum,from about 0.5% to about 9% by weight of tungsten, from about 0.5% toabout 10% by weight of zirconium, from about 41% to about 79% by weightof niobium and from about 50 ppm to about 300 ppm oxygen.